Xilio Therapeutics to Present Preclinical Data Highlighting Anti-Tumor Activity and Tolerability of XTX202 at the 2021 ASCO Annual Meeting

On May 20, 2021 Xilio Therapeutics, a biotechnology company developing tumor-selective immuno-oncology therapies for patients with cancer, reported the presentation of data from preclinical studies of XTX202, its tumor-selective interleukin-2 (IL-2) product candidate, demonstrating selective anti-tumor activity and favorable tolerability with no systemic toxicity observed (Press release, Xilio Therapeutics, MAY 20, 2021, View Source [SID1234580385]). The data will be reported in a poster entitled "XTX202, a protein-engineered IL-2, exhibits tumor-selective activity in mice without peripheral toxicities in non-human primates" at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The poster will be made available on the ASCO (Free ASCO Whitepaper) Annual Meeting website at the start of the meeting on June 4, 2021 at 9am ET.

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Xilio is leveraging its proprietary platform to engineer novel molecules that are designed to be activated in the tumor microenvironment (TME) and have the potential to result in localized, tumor-selective clinical activity without dose-limiting toxicities. XTX202, Xilio’s lead cytokine product candidate, is an engineered form of IL-2 that is masked with a protein domain to prevent binding activity until cleaved off by TME-associated proteases.

"The power of IL-2 to activate the immune system as a cancer therapeutic is promising, but utility of IL-2 agents has historically been greatly reduced due to toxicities," said Rónán O’Hagan, Ph.D., chief scientific officer of Xilio. "We have engineered XTX202 to overcome those challenges, with key features designed to ensure it is released and activated locally within the TME, where it selectively binds to IL-2 receptors on immune cells. We are excited to present these data which, for the first time, demonstrate selective tumor-inhibition and favorable tolerability of XTX202 in preclinical models. With these data, we plan to complete IND-enabling studies and submit an IND application in the second half of 2021 to evaluate XTX202 in patients with solid tumors."

Data reported in the poster are from preclinical studies in both mouse and non-human primate (NHP) models, including comparisons between XTX202 and XTX200, a non-masked, parent version of XTX202, as well as aldesleukin, a synthetic form of IL-2 approved for certain cancer indications by the U.S. Food and Drug Administration. Key data include:

XTX202, in its masked form, did not bind to IL-2 receptors, and matrix metalloproteinase (MMP) activation of XTX202 restored full binding to IL-2 receptor beta that is found on immune activating CD8 T cells and natural killer cells, illustrating the tight, protease-dependent control of IL-2 activity conferred by XTX202.
XTX202 was engineered to eliminate binding to IL-2Ra in order to enhance immune activation by CD8 T cells and NK cells, and to minimize immune suppression by regulatory T cells. No binding to IL-2Ra was detectable even after MMP-dependent activation of XTX202.
XTX202 inhibited tumor growth in syngeneic mouse models as a single agent with no evidence of toxicity or peripheral immune activation, thus demonstrating tumor selective activity.
XTX202 matched the tumor growth inhibition activity of aldesleukin and the non-masked control XTX200, without activation of immune response outside the TME, thereby avoiding the body weight loss in mice that was associated with doses of XTX200 or aldesleukin required for tumor growth inhibition.
XTX202 was well-tolerated in repeat dose studies in NHPs at doses up to 30 mg/kg.
XTX202 is estimated to have a greater than 100-fold improvement in therapeutic index compared to aldesleukin.

GammaDelta Therapeutics Receives FDA Clearance of IND Application for GDX012, a Novel Allogeneic Variable Delta 1 Gamma-delta T Cell Cancer Therapy

On May 20, 2021 GammaDelta Therapeutics ("GammaDelta"), a company focussed on exploiting the unique properties of gamma delta (γδ) T cells for immunotherapy, reported the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for the Company’s allogeneic variable delta 1 (Vδ1) gamma-delta (γδ) T cell therapy, GDX012, to be investigated as a treatment for haematological malignancies (Press release, GammaDelta Therapeutics, MAY 20, 2021, View Source [SID1234580384]). The FDA also granted orphan drug designation to allogeneic Vδ1 γδ T cell therapy (GDX012) for the treatment of Acute Myeloid Leukaemia (AML).

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Dr. Paolo Paoletti, CEO of GammaDelta Therapeutics, commented: "The clearance of our IND application for GDX012 marks an important step for our company in establishing a portfolio of innovative allogeneic cell therapies. The unique properties of Vδ1 γδ T cells will be evaluated for the first time in a clinical study for patients with AML. This important milestone results from our efforts to establish a robust pipeline of cellular immunotherapies derived from our proprietary platforms and processes for the isolation and expansion of Vδ1 γδ T cells from both blood and tissues for targeting haematological malignancies and solid tumours."

GammaDelta plans to initiate a Phase 1 clinical trial for patients with measurable residual disease (MRD) positive AML. Expected to begin later in 2021 as a multicentre study in the US, the trial will evaluate safety, tolerability and anti-leukemic activity of GDX012. GammaDelta Therapeutics is advancing its novel T cell platform under an ongoing collaboration with Takeda Pharmaceutical Company Limited ("Takeda") formed in 2017.

Dr. Michael Koslowski, Head of R&D and Chief Medical Officer of GammaDelta Therapeutics, said: "Although progress has been made in the treatment of AML, the median overall five-year survival rate for patients diagnosed with AML remains under 30 percent. With the development of GDX012 we are aiming to change the treatment paradigm for AML and potentially other haematologic malignancies. The unique biological characteristics of Vδ1 γδ T cells offer a first-in-class Vδ1 γδ T cell therapy for AML, where the development of cell therapies has been historically limited due to the lack of specific targets."

Dr. Chris Arendt, Oncology Therapeutic Area Unit Head of Takeda, commented: "The progression of GammaDelta Therapeutics’ platform technology underscores the potential of γδ T cells and the power of the innate immune system. Through collaboration with pioneers like GammaDelta Therapeutics, we hope to advance next-generation cell therapies and to maximise off-the-shelf treatments in the battle against hard-to-treat cancers."

GammaDelta has developed proprietary technologies to generate both blood-and tissue-derived allogeneic immunotherapies based on Vδ1 γδ T cells for the treatment of haematologic malignancies and solid tumours. Both platforms have enabled the creation of highly active and selective non-engineered and genetically engineered allogeneic cell therapies, which demonstrate cellular activity and tumour cell killing capacity. Vδ1 γδ T cells are a unique subset of T cells that specifically recognise and are activated by molecular patterns of dysregulation on cancer cells. The non-MHC-restricted activity of Vδ1 γδ T cells makes them a unique cell type for the development of fully allogeneic, "off-the-shelf" cell therapies.

Crescendo Biologics announces initiation of Phase 1 study of CB307 in patients with advanced, PSMA-positive solid tumours

On May 20, 2021 Crescendo Biologics Ltd (Crescendo), a clinical stage immuno-oncology company developing novel, targeted T cell enhancing therapeutics, reported that the first patient has entered the POTENTIA trial, a Phase 1, open-label, monotherapy study of CB307, the most advanced Humabody in Crescendo’s portfolio of T cell enhancers (Press release, Crescendo Biologics, MAY 20, 2021, View Source [SID1234580383]).

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CB307 is a unique, half-life extended Humabody targeting prostate-specific membrane antigen (PSMA) and the potent co-stimulatory molecule CD137 (4-1BB). Monospecific monoclonal antibodies against CD137 have been shown to enhance T cell activity in clinical studies as a cancer therapy, and CB307 is designed to enable potent, conditional and tumour-specific T cell activation whilst avoiding systemic toxicity.

The POTENTIA trial is a Phase 1, multi-centre, non-randomised study of CB307 in patients with advanced and/or metastatic PSMA-positive solid tumours. The study is designed to recruit up to 50 patients across dose escalation and expansion cohorts. The primary endpoint of the trial is to assess the safety and tolerability of CB307 and to determine the maximum tolerated dose.

Additional endpoints include initial evaluation of clinical efficacy, and the trial also includes a comprehensive panel of pharmacokinetic and other translational endpoints. Initial data from the dose escalation part of the trial are expected to be presented at a medical conference in 2022.

More information about the POTENTIA trial can be found on clinicaltrials.gov via NCT04839991 and in the poster recently presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2021.

Dr Kenji Hashimoto, Chief Medical Officer of Crescendo Biologics, said: "Recent clinical data have provided important validation for both PSMA and CD137 as therapeutic targets. We are therefore delighted to have initiated the CB307 clinical programme with our investigators. CB307 is a unique immuno-oncology therapy which we believe has potential to bring significant benefit to people suffering from hard-to-treat cancers."

Theodora Harold, Chief Executive Officer of Crescendo Biologics, added: "The initiation of the POTENTIA trial is an important milestone for Crescendo as it marks the beginning of clinical development of the first product candidate in our proprietary pipeline of T cell enhancing Humabody therapeutics. We have reached this point thanks to the dedication and focus of the Crescendo team, and we look forward to applying the data emerging from this trial to guide future clinical programmes."

TRACON Pharmaceuticals Announces Poster Presentations at the 2021 ASCO Virtual Annual Meeting

On May 20, 2021 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported the presentation of two abstracts at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 annual meeting, being held virtually June 4-8, 2021 (Press release, Tracon Pharmaceuticals, MAY 20, 2021, View Source [SID1234580380]).

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Poster Presentation:
Abstract Title: ENVASARC: A Pivotal Trial of Envafolimab, and Envafolimab in Combination with Ipilimumab, in Patients with Advanced or Metastatic Undifferentiated Pleomorphic Sarcoma or Myxofibrosarcoma who have Progressed on Prior Chemotherapy
Abstract Number: TPS11581
Poster Session: Sarcoma
Session Start: June 4, 2021 9:00AM EDT

Poster Discussion Session:
Abstract Title: Preliminary safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of Uliledlimab (TJ004309), a differentiated CD73 antibody, in combination with atezolizumab in patients with advanced cancer
Abstract Number: 2511
Poster Session: Development Therapeutics-Immunotherapy
Session Start: June 4, 2021 9:00AM EDT
The posters will be available on the publications page of the company’s website following presentation.

About Envafolimab

Envafolimab (KN035), a novel, single-domain antibody against PD-L1, is the first subcutaneously injected PD-(L)1 inhibitor to be studied in pivotal trials. Envafolimab is currently being studied in the ENVASARC Phase 2 pivotal trial in the U.S. sponsored by TRACON, has been studied in a completed Phase 2 pivotal trial as a single agent in MSI-H/dMMR advanced solid tumor patients in China and is being studied in an ongoing Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China, with both Chinese trials sponsored by 3D Medicines. TRACON’s partners Alphamab Oncology and 3D Medicines submitted an NDA to the NMPA in China for envafolimab in MSI-H/dMMR cancer that was accepted for review in December 2020 and granted priority review in January 2021. In the Phase 2 MSI-H/dMMR advanced solid tumor trial, the confirmed objective response rate (ORR) by blinded independent central review in MSI-H/dMMR colorectal cancer (CRC) patients treated with envafolimab who failed a fluoropyrimidine, oxaliplatin and irinotecan was 32%, which was similar to the 28% confirmed ORR reported in the Opdivo package insert in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin, and irinotecan and the 33% confirmed ORR reported for Keytruda in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin and irinotecan in cohort A of the KEYNOTE-164 clinical trial.

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multi-center, open label, randomized, non-comparative, parallel cohort study at approximately 25 top cancer centers in the United States that began dosing in December 2020. TRACON expects the trial to enroll 160 patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor, with 80 patients enrolled into cohort A of treatment with single agent envafolimab and 80 patients enrolled in cohort B of treatment with envafolimab and Yervoy. The primary endpoint is ORR by blinded independent central review with duration of response a key secondary endpoint.

About TJ004309

TJ004309 is a novel, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine, which is highly immunosuppressive. TJ004309 is currently being studied in an ongoing Phase 1 trial to assess safety and preliminary efficacy as a single agent and when combined with the PD-L1 checkpoint inhibitor Tecentriq in patients with advanced solid tumors.

Replimune Reports Fiscal Fourth Quarter and Year-Ended 2021 Financial Results and Provides Corporate Update

On May 20, 2021 Replimune Group, Inc. (NASDAQ: REPL), a biotechnology company developing a series of oncolytic immuno-gene therapies derived from its Immulytic platform, reported financial results for the fiscal fourth quarter and year ended March 31, 2021 and provided a business update (Press release, Replimune, MAY 20, 2021, View Source [SID1234580379]).

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"We have made good progress advancing our programs over the quarter and look forward to providing a data update with RP1 and RP2 at our virtual investor event being held in June as we continue to enroll into our registration-directed clinical trials in CSCC and anti-PD1 failed melanoma, with expected readouts in 2022," said Philip Astley-Sparke, CEO of Replimune. "Our vision extends well beyond our initial lead skin cancer indications, with the broader aim of becoming a cornerstone for immuno-oncology treatments across a wide spectrum of tumor types. With this in mind, and as we move closer to market, we recently expanded our senior management team with two key hires with a considerable track record of success in bringing multiple high profile programs to BLA approval and in overseeing the launch of new drugs in the immuno-oncology space."

Corporate Updates

Expanded management team with key hires to prepare for the transition to a commercial company. The Company hired Sushil Patel, Ph.D. as Chief Commercial Officer, arriving from Genentech where he was the head of their global oncology franchise for lung cancer, skin cancer and rare / agnostic tumor types, and previously the lifecycle leader in lung cancer for the multi-billion-dollar checkpoint blockade drug Tecentriq. In addition to hiring Dr. Patel, the Company also appointed Tanya Lewis as Chief Development Operations Officer. Ms. Lewis’s past accomplishments include successful negotiations related to registration trial designs, approval, and/or commercialization of XPOVIO, VELCADE, VARUBI, INTEGRILIN and ZEJULA.

Announced plans to amend the CERPASS clinical trial protocol to add complete response (CR) rate as an additional independent primary endpoint. The amendment is based on the depth and durability of responses and the manageable safety profile seen in patients with non-melanoma skin cancers treated with RP1 in combination with Opdivo to date. Under the modified clinical trial protocol for CERPASS, Replimune plans to add CR rate as an additional independent primary endpoint, in addition to overall response rate (ORR), and to reduce target enrollment from 240 patients to 180 patients. Secondary endpoints will continue to include duration of response, progression-free survival (PFS), and overall survival (OS). Replimune plans to submit the amended protocol to the FDA by the end of this quarter and is maintaining its guidance to expect primary data read out in 2022.

Held Type B meeting with the FDA to discuss the regulatory pathway for RP1 in combination with Opdivo (nivolumab) in anti-PD1 failed melanoma. Replimune recently held a Type B meeting with the FDA to discuss the design of the currently enrolling 125-patient registration-directed cohort of patients with anti-PD1 failed melanoma in the IGNYTE clinical trial. The FDA expressed that while a randomized controlled clinical trial would always be preferred for registration, if the clinical data is sufficiently compelling in this patient population with no clear standard of care, then the data could be submitted to the FDA for review under the accelerated approval pathway. The FDA also indicated that a randomized confirmatory trial would be needed as is required under the accelerated approval process.

Presented new biomarker and pre-clinical data for RP1 and RP2, at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The data presented continues to confirm potent anti-tumor activity and activation of robust systemic immune activation by RP1 and RP2.

Virtual Investor Event to be held on Thursday, June 3, 2021. The Company will host a virtual investor event to present updated data from its Phase 2 skin cancer cohorts combining RP1 with Opdivo and data from its Phase 1 study of RP2 alone and in combination with Opdivo. The event will include presentations by the management team and Mark Middleton, Professor of Experimental Cancer Medicine in the Department of Oncology, consultant Medical Oncologist at the Oxford Cancer and Hematology Centre and Head of the Department of Oncology at the University of Oxford.

First RP1 batches produced and filled at state-of-the-art manufacturing facility. Release testing is underway for the first GMP RP1 batches produced at its 63,000-square-foot manufacturing facility in Framingham, MA, that was built to support the commercialization of all of its products. Technology transfer for RP2 has also commenced and is expected to complete in the next quarter.
Program Highlights and Upcoming Milestones

RP1 in combination with Libtayo (cemiplimab) in CSCC: CERPASS, the Company’s Phase 2, global, randomized, controlled, registration-directed clinical trial continues to actively enroll patients and remains on track for a primary data read out in 2022.

RP1 in combination with Opdivo in anti-PD-1 failed melanoma: The Company’s 125-patient cohort in the IGNYTE Phase 2 clinical trial of RP1 in combination with Opdivo, continues to actively enroll patients and remains on track to report the primary data read out in 2022.

RP1 in combination with Opdivo in melanoma and non-melanoma skin cancers (NMSC): Following a positive Phase 2 data update in October 2020 and enrollment of the initial melanoma cohort (including anti-PD1 naïve and anti-PD1 failed patients) being complete, the Company continues to enroll its 45-patient cohort evaluating RP1 in combination with Opdivo in NMSC. The Company plans to provide an update on these programs at its June 3rd investor event.

RP1 in anti-PD1 failed NSCLC: The first patient in the cohort of 30 anti-PD1 failed NSCLC patients treated with RP1 combined with Opdivo has been dosed, and the Company expects to report initial data in the second half of 2021.

RP1 as monotherapy in solid organ transplant recipients with CSCC: The Company is currently enrolling a 30 patient Phase 1b clinical trial (ARTACUS) assessing the safety and efficacy of RP1 in liver and kidney transplant recipients with CSCC. Enrollment in this immuno-compromised population has been hampered by COVID 19, but as the effects of the pandemic reduce the Company expects recruitment to increase. Early data from this clinical trial is intended to be presented in the second half of 2021.

RP1 in combination with Opdivo in MSI-H/dMMR tumors: The Company continues to expect to be able to decide whether to pursue RP1 for MSI-H/dMMR tumors into registration-directed development by the end of 2021.

RP2 alone and in combination with Opdivo: Following positive data with RP2 given as monotherapy that were presented in October 2020, the Company is actively enrolling a 30-patient cohort evaluating RP2 in combination with Opdivo. Updated data from this clinical trial, including an update on patients treated with RP2 monotherapy and initial data with RP2 in combination with Opdivo will be presented at the upcoming June 3rd investor event.

RP3 alone and in combination with anti-PD-1 therapy: The Phase 1 clinical trial evaluating RP3 alone and in combination with anti-PD1 therapy in solid tumor patients is actively enrolling and the Company remains on track to report initial data in the second half of 2021.

Target evaluation for new indications is currently underway: The Company remains on track to disclose part of its initial development plans for RP2 and/or RP3 in less immune responsive tumor types at the upcoming June 3rd investor event.
Financial Fiscal Quarter Four and Year End Highlights:

Cash Position: As of March 31, 2021, cash, cash equivalents and short-term investments were $476.3 million, as compared to $168.6 million as of March 31, 2020. This increase was primarily related to $372.5 million in net proceeds from financing activities offset by an increase in cash utilized in operating activities in advancing our expanded clinical development plan.

Based on the current operating plan, Replimune believes that existing cash and cash equivalents and short-term investments will fund operating expenses and capital expenditure requirements into the second half of 2024.
R&D Expenses: Research and development expenses were $16.2 million for the fourth quarter and $56.8 million for the fiscal year ended March 31, 2021, as compared to $11.2 million for the fourth quarter and $38.8 million for the fiscal year ended March 31, 2020. This increase was primarily due to clinical expenses driven by the company’s lead programs, expansion into additional studies, operating our dedicated manufacturing facility and related increased personnel costs. Research and development expenses included $2.0 million in stock-based compensation expenses for the fourth quarter and $5.7 million in stock-based compensation expenses for the fiscal year ended March 31, 2021.

G&A Expenses: General and administrative expenses were $6.0 million for the fourth quarter and $23.2 million for the fiscal year ended March 31, 2021, as compared to $5.2 million for the fourth quarter and $17.4 million for the year ended March 31, 2020. The increase was primarily driven by personnel related costs, professional fees, and facility expansion. General and administrative expenses included $1.5 million in stock-based compensation expenses for the fourth quarter and $6.0 million in stock-based compensation expenses for the fiscal year ended March 31, 2021.

Net Loss: Net loss was $21.5 million for the fourth quarter and $80.9 million for the fiscal year ended March 31, 2021, as compared to a net loss of $15.8 million for the fourth quarter and $52.6 million for the fiscal year ended March 31, 2020.
About CERPASS
CERPASS is Replimune’s registration-directed randomized, global Phase 2 clinical study to compare the effects of Libtayo alone versus a combination of Libtayo and Replimune’s investigational oncolytic immunotherapy RP1. The clinical trial will enroll 180 patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are naïve to anti-PD1 therapy. The trial will evaluate complete response (CR) rate and overall response rate (ORR) as its two primary efficacy endpoints as assessed by independent review, as well as duration of response, progression-free survival (PFS), and overall survival (OS) as its secondary endpoints. The study is being run under a clinical trial collaboration agreement with Regeneron in which the costs of the trial are shared and full commercial rights retained by Replimune. Libtayo is being jointly developed by Regeneron and Sanofi.
Libtayo is a registered trademark of Regeneron.

About IGNYTE
IGNYTE is Replimune’s multi-cohort Phase 1/2 trial of RP1 plus Opdivo. There are 4 tumor specific cohorts currently enrolling in this trial including a 125-patient extension cohort of RP1 combined with Opdivo in anti-PD-1 failed cutaneous melanoma. This cohort was initiated after completing enrollment in a prior Phase 2 cohort in the same trial of approximately 30 patients with melanoma. The additional thirty patient cohorts are studying RP1 in combination with Opdivo in non-melanoma skin cancers which includes both naïve and anti-PD-1 failed CSCC, in microsatellite instability high, or MSI-H/dMMR tumor types and anti-PD-1 failed non-small cell lung cancer, or NSCLC. This trial is being done under a collaboration and supply agreement with Bristol Myer Squibb.
Opdivo is a registered trademark of Bristol-Myers Squibb Company.

About RP1
RP1 is Replimune’s lead Immulytic product candidate and is based on a proprietary new strain of herpes simplex virus engineered to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response.

About RP2 & RP3
RP2 and RP3 are derivatives of RP1 that express additional proteins. RP2 expresses an anti-CTLA-4 antibody-like molecule and RP3 additionally expresses the immune co-stimulatory pathway activating proteins CD40L and 4-1BBL. RP2 and RP3 are intended to provide targeted and potent delivery to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic immune-based efficacy on tumors and limiting off-target toxicity.